Scientists Closer to Finding Genes that Affect Prostate Cancer Risk

WINSTON-SALEM, N.C. – Scientists believe they are on track for finding a gene, or genes, that can increase prostate cancer risk for some men – and have new evidence that a particular gene variant can reduce risk for others – putting researchers one step closer to being able to predict disease risk in individual men.

The two studies are reported by researchers from Wake Forest University Baptist Medical Center and colleagues in the current issue of the Journal of the National Cancer Institute.

“These two studies are a step forward in understanding the mechanism of prostate cancer,” said Jianfeng Xu, M.D., Dr. PH, a genetic researcher at Wake Forest Baptist. “We believe they point to a future where at-risk men can be identified early.”

Prostate cancer is the second-leading cause of cancer deaths among men in the United States. In 2003, an estimated 220,000 new prostate cancer cases were diagnosed. More than 28,000 deaths are expected to result annually from this disease. Age, race and family history are the strongest and most consistently observed risk factors for the disease. In fact, the genetic predisposition to prostate cancer is the strongest among all common cancers.

In the largest study to date looking for the likely link between genes and prostate cancer, scientists found strong evidence for a prostate cancer gene at chromosome 17. The sheer size of the study would make any findings significant. However, these results are especially important because chromosome 17 is known to harbor a breast cancer gene, BRCA1, which has also been suggested to play a role in prostate cancer risk in men.

This was a collaborative project of Wake Forest Baptist, the National Human Genome Research Institute of the National Institutes of Health, the Translational Genomics Research Institute, Johns Hopkins Medical Institutions, the University of Michigan, Umea University in Sweden and the University of Tampere in Finland.

Previous studies, including studies by Wake Forest Baptist, have identified at least five possible prostate cancer susceptibility genes. There has been difficulty confirming the genes because of the likelihood that there are several different genes that increase risk and the need to test a large number of high-risk families to get reliable results.

In this study, the scientists set out to overcome some of these problems by combining data from four previous studies. They tested a total of 426 families – from North America and Scandinavian countries – who have high rates of prostate cancer.

Using blood samples from participants, the scientists conducted a genetic linkage study, also called genetic mapping. This process looks at a large number of genetic markers with the goal of finding a handful of markers that tend to occur in people with the disease. This method works because researchers are able to trace these markers as they are passed down through families. In this way, the genetic markers serve as indicators that a prostate cancer gene is located nearby.

“This is the largest scan for prostate cancer susceptibility genes to date,” said Xu. “We found multiple pieces of evidence to suggest the presence of a prostate cancer gene, or genes, on chromosome 17. These results offer renewed interest, excitement and confidence in the genetic linkage studies of prostate cancer.”

In a separate study of a gene involved in inflammation, they found that a variant is associated with a decreased risk for prostate cancer – men without the variant were 19 percent more likely to develop familial prostate cancer than those who had it. This second study was based on the theory that inflammation is important in the development of prostate cancer, just as it is for colon cancer. The work is a collaboration of Wake Forest Baptist, Umea University and Johns Hopkins.

The research involved 1,383 Swedish men with prostate cancer and 780 who didn’t have the disease. The researchers examined four different variants of the MIC-1 (macrophage-inhibitory cytokine-1) gene, which is involved in inflammation. One of the variants was associated with a significantly reduced risk (7 percent for sporadic cancer and 19 percent for familial cancer).

“This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility,” wrote the researchers in their report.

About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The system comprises 1,282 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of “America’s Best Hospitals” by U.S. News & World Report.

In The News

On March 20, seniors at Wake Forest School of Medicine learned where they will begin their careers as doctors at Match Day,an annual event at which graduating medical students learn where they’ll be doing their residencies. This year 113 Wake Forest medical students, 59 men and 54 women, matched in 20 specialties.

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